ZA200402812B - Imidazo (4,3-e)-1,2,4-triazolo(1,5-c) pyrimidines as adenosine A2a receptor antagonists. - Google Patents
Imidazo (4,3-e)-1,2,4-triazolo(1,5-c) pyrimidines as adenosine A2a receptor antagonists. Download PDFInfo
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- ZA200402812B ZA200402812B ZA200402812A ZA200402812A ZA200402812B ZA 200402812 B ZA200402812 B ZA 200402812B ZA 200402812 A ZA200402812 A ZA 200402812A ZA 200402812 A ZA200402812 A ZA 200402812A ZA 200402812 B ZA200402812 B ZA 200402812B
- Authority
- ZA
- South Africa
- Prior art keywords
- alkyl
- alkoxy
- compound
- phenyl
- group
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Classifications
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- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/14—Ortho-condensed systems
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/582—Recycling of unreacted starting or intermediate materials
Landscapes
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| US32956701P | 2001-10-15 | 2001-10-15 |
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| ZA200402812B true ZA200402812B (en) | 2005-04-25 |
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| EP (1) | EP1435960B1 (es) |
| JP (2) | JP4545437B2 (es) |
| KR (1) | KR100687954B1 (es) |
| CN (1) | CN100421663C (es) |
| AR (1) | AR037243A1 (es) |
| AU (1) | AU2002340184B2 (es) |
| CA (1) | CA2463598C (es) |
| HU (1) | HUP0401777A3 (es) |
| IL (1) | IL160878A0 (es) |
| MX (1) | MXPA04003474A (es) |
| MY (1) | MY124864A (es) |
| NZ (1) | NZ531761A (es) |
| PE (1) | PE20030477A1 (es) |
| WO (1) | WO2003032996A1 (es) |
| ZA (1) | ZA200402812B (es) |
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|---|---|---|---|---|
| US6875772B2 (en) * | 2001-11-30 | 2005-04-05 | Schering Corporation | [1,2,4]-Triazole bicyclic adeonsine A2a receptor antagonists |
| US20040127510A1 (en) * | 2002-04-16 | 2004-07-01 | Heintzelman Geoffrey R. | Arylindenopyridines and arylindenopyrimidines and related therapeutic and prophylactic methods |
| CN101310724A (zh) | 2002-12-19 | 2008-11-26 | 先灵公司 | 腺苷A2a受体拮抗剂的应用 |
| PT1622912E (pt) | 2003-04-23 | 2009-08-17 | Schering Corp | Antagonistas 2-alcinil- e 2-alcenilpirazolo-[4,3-b]-1,2,4- triazolo-[1,5-c]-pirimidina do receptor a2a da adenosina |
| EP1631294B1 (en) * | 2003-06-10 | 2010-09-15 | Kyowa Hakko Kirin Co., Ltd. | A method of treating an anxiety disorder |
| PL380665A1 (pl) * | 2003-12-19 | 2007-03-05 | Schering Corporation | Farmaceutyczne kompozycje |
| ES2342082T3 (es) | 2004-04-21 | 2010-07-01 | Schering Corporation | Antagonistas de receptores a2a de adenosina de pirazolo(4,3-e)-1,2,4-triazolo(1,5-c)pirimidina. |
| ATE556712T1 (de) * | 2005-06-07 | 2012-05-15 | Kyowa Hakko Kirin Co Ltd | A2a antagonisten zur behandlung von motorischen störungen |
| CN101312978A (zh) | 2005-09-19 | 2008-11-26 | 先灵公司 | 作为腺苷A2a受体拮抗剂的2－杂芳基－吡唑并－[4,3－e]－1,2,4－三唑并－[1,5－c]－嘧啶 |
| AR056080A1 (es) | 2005-09-23 | 2007-09-19 | Schering Corp | 7-[2-[4-(6-fluoro-3-metil-1,2-benciosoxazol-5-il)-1-piperazinil]etil]-2-(1-propinil)-7h-pirazol-[4,3-e]-[1,2,4]-triazol-[1,5-c] -pirimidin-5-amine |
| ES2273599B1 (es) | 2005-10-14 | 2008-06-01 | Universidad De Barcelona | Compuestos para el tratamiento de la fibrilacion auricular. |
| TW200817039A (en) * | 2006-10-06 | 2008-04-16 | Dynamis Therapeutics Inc | Compositions and methods for skin lightening |
| EP2125750B1 (en) * | 2007-02-26 | 2014-05-21 | Vitae Pharmaceuticals, Inc. | Cyclic urea and carbamate inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| US7691869B2 (en) | 2007-03-30 | 2010-04-06 | King Pharmaceuticals Research And Development, Inc. | Pyrrolotriazolopyrimidine derivatives, pharmaceutical compositions containing them and methods of treating conditions and diseases mediated by the adenosine A2A receptor activity |
| ATE554078T1 (de) * | 2007-07-26 | 2012-05-15 | Vitae Pharmaceuticals Inc | Synthese von 11-beta-hydroxysteroid-dehydrogenase-1-hemmern |
| AR069207A1 (es) * | 2007-11-07 | 2010-01-06 | Vitae Pharmaceuticals Inc | Ureas ciclicas como inhibidores de la 11 beta - hidroxi-esteroide deshidrogenasa 1 |
| WO2009075835A1 (en) | 2007-12-11 | 2009-06-18 | Vitae Pharmaceutical, Inc | CYCLIC UREA INHIBITORS OF 11β-HYDROXYSTEROID DEHYDROGENASE 1 |
| TW200934490A (en) * | 2008-01-07 | 2009-08-16 | Vitae Pharmaceuticals Inc | Lactam inhibitors of 11 &abgr;-hydroxysteroid dehydrogenase 1 |
| US8592409B2 (en) | 2008-01-24 | 2013-11-26 | Vitae Pharmaceuticals, Inc. | Cyclic carbazate and semicarbazide inhibitors of 11β-hydroxysteroid dehydrogenase 1 |
| JP5734666B2 (ja) * | 2008-02-11 | 2015-06-17 | ヴァイティー ファーマシューティカルズ，インコーポレイテッド | １１β−ヒドロキシステロイドデヒドロゲナーゼ１の１，３−オキサアゼパン−２−オン及び１，３−ジアゼパン−２−オン阻害剤 |
| JP5730021B2 (ja) * | 2008-02-15 | 2015-06-03 | ヴァイティー ファーマシューティカルズ，インコーポレイテッド | １１β−ヒドロキシステロイドデヒドロゲナーゼ１の阻害剤としてのシクロアルキルラクタム誘導体 |
| EP2262811B1 (en) | 2008-03-04 | 2016-04-27 | Merck Sharp & Dohme Corp. | 1,2,4-triazolo[4,3-c]pyrimidin-3-one and pyrazolo [4,3-e]-1,2,4-triazolo [4,3-c]pyrimidin-3-one compounds for use as adenosine a2a receptor antagonists |
| JP5538356B2 (ja) * | 2008-03-18 | 2014-07-02 | ヴァイティー ファーマシューティカルズ，インコーポレイテッド | １１β−ヒドロキシステロイドデヒドロゲナーゼ１型の阻害剤 |
| AR071609A1 (es) * | 2008-05-01 | 2010-06-30 | Vitae Pharmaceuticals Inc | Inhibidores ciclicos de 11(beta) -hidroxiesteroide deshidrogenasa 1 |
| CA2723032A1 (en) * | 2008-05-01 | 2009-11-05 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| AR071236A1 (es) | 2008-05-01 | 2010-06-02 | Vitae Pharmaceuticals Inc | Inhibidores ciclicos de la 11beta-hidroxiesteroide deshidrogenasa 1 |
| EP2291370B1 (en) | 2008-05-01 | 2013-11-27 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| CA2730499A1 (en) | 2008-07-25 | 2010-01-28 | Boehringer Ingelheim International Gmbh | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| WO2010010157A2 (en) | 2008-07-25 | 2010-01-28 | Boehringer Ingelheim International Gmbh | INHIBITORS OF 11beta-HYDROXYSTEROID DEHYDROGENASE 1 |
| EP2393807B1 (en) | 2009-02-04 | 2013-08-14 | Boehringer Ingelheim International GmbH | Cyclic inhibitors of 11 -hydroxysteroid dehydrogenase 1 |
| TW201039034A (en) * | 2009-04-27 | 2010-11-01 | Chunghwa Picture Tubes Ltd | Pixel structure and the method of forming the same |
| MA33216B1 (fr) | 2009-04-30 | 2012-04-02 | Boehringer Ingelheim Int | Inhibiteurs cycliques de la 11béta-hydroxysteroïde déshydrogénase 1 |
| US20100331320A1 (en) * | 2009-04-30 | 2010-12-30 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| EP2440537A1 (en) | 2009-06-11 | 2012-04-18 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 based on the 1,3 -oxazinan- 2 -one structure |
| US8883778B2 (en) | 2009-07-01 | 2014-11-11 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11 beta-hydroxysteroid dehydrogenase 1 |
| EP2582698B1 (en) | 2010-06-16 | 2016-09-14 | Vitae Pharmaceuticals, Inc. | Substituted 5-,6- and 7-membered heterocycles, medicaments containing such compounds, and their use |
| EP2585444B1 (en) | 2010-06-25 | 2014-10-22 | Boehringer Ingelheim International GmbH | Azaspirohexanones as inhibitors of 11-beta-hsd1 for the treatment of metabolic disorders |
| US9006177B2 (en) * | 2010-09-24 | 2015-04-14 | Advinus Therapeutics Limited | Fused tricyclic compounds as adenosine receptor antagonist |
| WO2012059416A1 (en) | 2010-11-02 | 2012-05-10 | Boehringer Ingelheim International Gmbh | Pharmaceutical combinations for the treatment of metabolic disorders |
| WO2015027431A1 (en) | 2013-08-29 | 2015-03-05 | Merck Sharp & Dohme Corp. | 2,2-difluorodioxolo a2a receptor antagonists |
| CR20210271A (es) | 2018-11-30 | 2021-07-14 | Merck Sharp & Dohme | Derivados de amino triazolo quinazolina 9-sustituidos como antagonistas del receptor de adenosina, composiciones farmacéuticas y su uso |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3677445D1 (de) | 1985-09-30 | 1991-03-14 | Ciba Geigy Ag | 2-substituierte-e-kondensierte(1,5-c)-pyrimidine, pharmazeutische zubereitungen und ihre verwendung. |
| DE3781080T2 (de) * | 1986-09-30 | 1992-12-24 | Ciba Geigy Ag | 2-substituierte-e-kondensierte(1,2,4)triazolo-(1,5-c)pyrimidine, pharmazeutische zubereitungen und ihre verwendung. |
| IT1264901B1 (it) | 1993-06-29 | 1996-10-17 | Schering Plough S P A | Analoghi eterociclici di 1,2,4-triazolo(15-c)pirimidine ad attivita' antagonista per il recettore a2 dell'adenosina |
| CA2144330A1 (en) | 1993-07-27 | 1995-02-09 | Fumio Suzuki | A therapeutic agent for parkinson's disease |
| IT1277392B1 (it) | 1995-07-28 | 1997-11-10 | Schering Plough S P A | Analoghi eterociclici di 1,2,4-triazolo(1,5-c]pirimidine ad attivita' antagonista per il recettore a2a dell'adenosina |
| IT1291372B1 (it) * | 1997-05-21 | 1999-01-07 | Schering Plough S P A | Uso di analoghi eterociclici di 1,2,4-triazolo (1,5-c) pirimidine per la preparazione di medicamenti utili per il trattamento delle malattie |
| KR100513062B1 (ko) | 1998-04-03 | 2005-09-05 | 가부시키 가이샤 오오쯔카 세이야쿠 고우죠우 | 트리아조로푸린 유도체, 그 유도체를 함유하는 의약조성물, 아데노신 에이3 수용체 친화제 및 천식치료제 |
| CN1207298C (zh) | 1999-09-28 | 2005-06-22 | 株式会社大塚制药工厂 | 三唑并嘌呤衍生物、含有该衍生物的药物组合物和腺苷a3受体亲和剂 |
| TWI288137B (en) | 2000-05-26 | 2007-10-11 | Schering Corp | Adenosine A2a receptor antagonists |
| CA2468649C (en) | 2001-11-30 | 2009-03-10 | Schering Corporation | Adenosine a2a receptor antagonists |
-
2002
- 2002-10-11 MX MXPA04003474A patent/MXPA04003474A/es active IP Right Grant
- 2002-10-11 JP JP2003535799A patent/JP4545437B2/ja not_active Expired - Fee Related
- 2002-10-11 CN CNB028203283A patent/CN100421663C/zh not_active Expired - Fee Related
- 2002-10-11 NZ NZ531761A patent/NZ531761A/en unknown
- 2002-10-11 EP EP02778530.2A patent/EP1435960B1/en not_active Expired - Lifetime
- 2002-10-11 KR KR1020047005369A patent/KR100687954B1/ko not_active IP Right Cessation
- 2002-10-11 AU AU2002340184A patent/AU2002340184B2/en not_active Ceased
- 2002-10-11 CA CA002463598A patent/CA2463598C/en not_active Expired - Fee Related
- 2002-10-11 IL IL16087802A patent/IL160878A0/xx unknown
- 2002-10-11 HU HU0401777A patent/HUP0401777A3/hu unknown
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- 2002-10-11 AR ARP020103834A patent/AR037243A1/es unknown
- 2002-10-11 PE PE2002001009A patent/PE20030477A1/es not_active Application Discontinuation
- 2002-10-11 US US10/269,754 patent/US6653315B2/en not_active Expired - Lifetime
- 2002-10-11 WO PCT/US2002/032630 patent/WO2003032996A1/en active IP Right Grant
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|---|---|
| KR20050035155A (ko) | 2005-04-15 |
| HUP0401777A2 (hu) | 2004-12-28 |
| CN100421663C (zh) | 2008-10-01 |
| WO2003032996A1 (en) | 2003-04-24 |
| KR100687954B1 (ko) | 2007-02-27 |
| JP2005506352A (ja) | 2005-03-03 |
| PE20030477A1 (es) | 2003-06-06 |
| JP2008297312A (ja) | 2008-12-11 |
| CA2463598A1 (en) | 2003-04-24 |
| US20030171381A1 (en) | 2003-09-11 |
| AR037243A1 (es) | 2004-11-03 |
| CN1612736A (zh) | 2005-05-04 |
| MXPA04003474A (es) | 2004-07-30 |
| EP1435960A1 (en) | 2004-07-14 |
| US6653315B2 (en) | 2003-11-25 |
| MY124864A (en) | 2006-07-31 |
| HUP0401777A3 (en) | 2008-06-30 |
| EP1435960B1 (en) | 2014-07-30 |
| AU2002340184B2 (en) | 2005-10-06 |
| CA2463598C (en) | 2009-09-08 |
| NZ531761A (en) | 2005-10-28 |
| JP4545437B2 (ja) | 2010-09-15 |
| IL160878A0 (en) | 2004-08-31 |
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